Familial cortical myoclonic tremor with epilepsy: TTTCA/TTTTA repeat expansions and expanding phenotype in two Chinese families

Recently, expanded intronic TTTCA and TTTTA repeat in SAMD12 were identified in families with familial cortical myoclonic tremor with epilepsy (FCMTE). We conducted to this study to clarify the genetic etiology and to describe the clinical, neurophysiologic, and imaging features in two unrelated Chinese families with FCMTE. In this study, we performed the RP-PCR and long-range PCR analysis to examine and verify TTTCA and TTTTA expansions in five affected members whose severities of cortical tremor, neuropsychology and MRI were also evaluated. Reliable clinical information was collected from another two affected members. Our results revealed that expansions of intronic TTTCA and TTTTA repeats in SAMD12 were both identified in all five affected subjects. All seven affected living patients had cortical tremor with a median age at onset of 16.4 years (range, 10–22 years). Convulsions occurred in 5 of 7 with a median age at onset of 32.4 years (range, 10–42 years). Among five patients evaluated for cortical tremor severity and psychiatric comorbidity, two patients had severe cortical tremor, anxiety and depression. Abnormal brain MRI findings including the possible existence of demyelination, severe atrophy of the cerebral hemisphere and abnormal bilateral symmetrical signals in the globus pallidus were observed in three patients, respectively. These results further expanded the known genotype in two Chinese families affected with FCMTE. Border clinical spectrum needs to be confirmed in future studies from additional FCMTE families genetically diagnosed.